title: Pharmacokinetics, safety and antiviral activity of fosamprenavir/ritonavir-containing regimens in HIV-infected children aged 4 weeks to 2 years-48-week study data.
abstract: BACKGROUND
  Pharmacokinetics, safety and antiviral activity of fosamprenavir (FPV) with ritonavir (RTV) twice daily were evaluated in HIV-1-infected infants and children 4 weeks to <2 years over 48 weeks.
  
  
  METHODS
  Results from intensive pharmacokinetic sampling of subjects enrolled in single dose visits was used to determine individualized dosing for the first 6-10 subjects in each of 2 cohorts (4 weeks to <6 months, 6 months to <2 years); steady state pharmacokinetic data were then used to select the dosage regimen for the remaining subjects recruited to the cohort. Intensive pharmacokinetic sampling was performed at week 2 or 8; predose samples were collected every 4-12 weeks thereafter. Safety and plasma HIV-1 RNA were monitored every 4-12 weeks.
  
  
  RESULTS
  Fifty-nine subjects received study medication. FPV 45 mg/kg boosted with RTV 7 to 10 mg/kg BID achieved average plasma amprenavir area under curve(0-τ) values 26% to 28% lower and Cmax similar to historical adult data for FPV/RTV 700/100 mg BID; amprenavir Cτ values were lower in the subjects <6 months of age. At week 48, 35 of 54 (65%) subjects had achieved plasma HIV-1 RNA <400 copies/mL and 33 of 54 (61%) had plasma HIV-1 RNA values <50 copies/mL. The most common adverse events were diarrhea, upper respiratory tract infection, gastroenteritis and otitis media.
  
  
  CONCLUSIONS
  Final FPV/RTV dosing regimens achieved plasma amprenavir exposures comparable with those from regimens approved in adults, with the exception of trough exposures in the <6-month-old infants. The FPV/RTV regimens led to viral suppression in 61% of patients and were generally well tolerated.
authors.affiliation: From the *Department of Pediatrics and Child Health, Children's Infectious Diseases Clinical Research Unit, Stellenbosch University, Tygerberg; †Perinatal HIV Research Unit, Johannesburg, South Africa; ‡Universidad Nacional Autonoma de Mexico, Mexico City, Mexico; §GlaxoSmithKline, Research Triangle Park, NC; and ¶GlaxoSmithKline, Uxbridge, United Kingdom.
authors.forename: Mark
authors.initials: M
authors.lastname: Cotton
authors.forename: Haseena
authors.initials: H
authors.lastname: Cassim
authors.forename: Noris
authors.initials: N
authors.lastname: Pavía-Ruz
authors.forename: Harmony P
authors.initials: HP
authors.lastname: Garges
authors.forename: Teodora
authors.initials: T
authors.lastname: Perger
authors.forename: Susan L
authors.initials: SL
authors.lastname: Ford
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Wire
authors.forename: Naomi
authors.initials: N
authors.lastname: Givens
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Ross
authors.forename: Yu
authors.initials: Y
authors.lastname: Lou
authors.forename: Jörg
authors.initials: J
authors.lastname: Sievers
authors.forename: Katharine
authors.initials: K
authors.lastname: Cheng
mesh_terms: D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D015331:Cohort Studies; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D008297:Male; D010755:Organophosphates / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019562:Viral Load / Q000187:drug effects
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D010755:Organophosphates; D012367:RNA, Viral; D013449:Sulfonamides; D019438:Ritonavir; C426859:fosamprenavir